Catalytic Palladium/Acid Zeolites Substitute Metal Reagents for the Industrial Alkylation of Aromatics: A Fragrance as a Representative Case

ABSTRACT

The functionalization of aromatic systems with carbon chains is among the most demanded transformations in fine chemistry, mostly performed with stochiometric metal reagents. Despite the development of a plethora of catalytic methods in recent years, most remain methodological rather than part of any applied reaction for industrial molecules. Here we show that the commercial fragrance Hivernal Neo (1,1‐dimethyl‐2,3‐dihydro‐1 H ‐indene‐ ar ‐propanal), whose synthesis is currently carried out with H ₂ SO ₄ and TiCl ₄ in stoichiometric amounts, can be prepared with catalytic amounts of acid zeolites (instead of H ₂ SO ₄ ) and palladium (instead of TiCl ₄ ), the latter through three different pathways with respect to reported methods: Heck reaction with ligandless subnanometric palladium clusters, Heck reaction coupled to allyl alcohol isomerization with well–defined palladium complexes, and direct C–H activation–coupling reaction with palladium and silver. These new approaches do not only offer a more sustainable pathway but also increase the overall yield for Hivernal Neo from 7% to approximately 30%, without significantly lengthening the sequential route (4–5 steps) with respect to previous methods. Failed synthetic routes are also described. This representative case is potentially extendable to other industrial substrates, offering a cheaper and more sustainable synthesis on the basis of green and techno–economic metrics.